Sickle cell disease (SCD) (also known as sickle cell anemia (SCA) and drepanocytosis) and (β-thalassemia are inherited blood disorders that are caused by mutations in the β-globin gene (HBB). Sickle cell disease is characterized by atypical hemoglobin molecules which can distort red blood cells into a sickle, or crescent, shape and lead to anemia. β-thalassemia is characterized by reduced amounts of hemoglobin and fewer circulating red blood cells than normal, which results in mild or severe anemia.
Sickle cell disease is the most common inherited single-gene disorder. One out of every 12 African-Americans carries the sickle cell allele, and one out of every 500 African-American children is born with sickle cell disease. Annually there are over 332,000 conceptions or births affected by sickle cell disease worldwide. Approximately 56,000 people are affected with a major thalassemia (αor β) worldwide (see, e.g., Piel, F. B., Nat Commun., 1(104): 1-7 (2010)).
Sickle cell disease has no widely available cure. Currently, allogeneic hematopoietic stem cell (HSC) transplantation, in which normal HSCs are harvested from a suitable donor and transplanted into a sickle cell disease patient, can cure sickle cell disease patients. However, suitable donors (often siblings) are found in only about 10% of sickle cell disease patients, and there is a significant risk of rejection and graft-versus host disease (GVHD). Blood and marrow stem cell transplants may offer a cure for a small number of people. Treatments for thalassemias depend on the type and severity of the disorder, but there is no general cure. Like sickle cell disease, allogeneic HSC transplantation is effective in a small percentage of patients.
Thus, there is a need for alternative treatments for diseases associated with mutations in the (β-globin gene, such as sickle cell disease and thalassemias. The invention provides such a treatment.